Diagnostic performance of a seven-marker serum protein biosignature for the diagnosis of active TB disease in African primary healthcare clinic attendees with signs and symptoms suggestive of TB

Chegou, Novel N.; Sutherland, Jayne S.; Malherbe, Stephanus T.; Crampin, Amelia C.; Corstjens, Paul L. A. M.; Geluk, Annemieke; Mayanja‐Kizza, Harriet; Loxton, André G.; Spuy, Gian D. van der; Stanley, Kim; Kotze, Leigh A.; Vyver, Marieta van der; Rosenkrands, Ida; Kidd, Martin; Helden, Paul D. van; Dockrell, Hazel M.; Ottenhoff, Tom H. M.; Kaufmann, Stefan H. E.; Walzl, Gerhard

doi:10.1136/thoraxjnl-2015-207999

Cited by 134 publications

(169 citation statements)

References 38 publications

(38 reference statements)

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“…The mean age of all study participants was 34.1±11.3 years and only one of the study participants was HIV positive. Using a pre-established diagnostic algorithm [12], 21 patients were classified as having TB disease. Of the 42 patients with other respiratory diseases (ORD), 21 were QFT-negative ( M. tuberculosis uninfected) while 21 individuals were latently infected (LTBI), as defined by a positive QFT-test using the manufacturer's recommended cut-off value (≥0.35 IU/ml).…”

Section: Resultsmentioning

confidence: 99%

“…Participants included in the present study were individuals presenting with signs and symptoms requiring investigation for TB, and were recruited as part of the recently concluded EDCTP-funded African European Tuberculosis Consortium (AE-TBC) study [12]. All study participants were recruited from a peripheral level health care centre, Fisantekraal, situated in the outskirts of Cape Town, South Africa.…”

Section: Methodsmentioning

confidence: 99%

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Detection of a combination of serum IgG and IgA antibodies against selected mycobacterial targets provides promising diagnostic signatures for active TB

et al. 2017

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Immunoglobulin G (IgG) based tests for the diagnosis of active tuberculosis (TB) disease often show a lack of specificity in TB endemic regions, which is mainly due to a high background prevalence of LTBI. Here, we investigated the combined performance of the responses of different Ig classes to selected mycobacterial antigens in primary healthcare clinic attendees with signs and symptoms suggestive of TB. The sensitivity and specificity of IgA, IgG and/or IgM to LAM and 7 mycobacterial protein antigens (ESAT-6, Tpx, PstS1, AlaDH, MPT64, 16kDa and 19kDa) and 2 antigen combinations (TUB, TB-LTBI) in the plasma of 63 individuals who underwent diagnostic work-up for TB after presenting with symptoms and signs compatible with possible active TB were evaluated. Active TB was excluded in 42 individuals of whom 21 has LTBI whereas active TB was confirmed in 21 patients of whom 19 had a follow-up blood draw at the end of 6-month anti-TB treatment. The leading single serodiagnostic markers to differentiate between the presence or absence of active TB were anti-16 kDa IgA, anti-MPT64 IgA with sensitivity and specificity of 90%/90% and 95%/90%, respectively. The combined use of 3 or 4 antibodies further improved this performance to accuracies above 95%. After successful completion of anti-TB treatment at month 6, the levels of 16 kDa IgA and 16 kDa IgM dropped significantly whereas LAM IgG and TB-LTBI IgG increased. These results show the potential of extending investigation of anti-tuberculous IgG responses to include IgM and IgA responses against selected protein and non-protein antigens in differentiating active TB from other respiratory diseases in TB endemic settings.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Detection of a combination of serum IgG and IgA antibodies against selected mycobacterial targets provides promising diagnostic signatures for active TB

et al. 2017

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“…The diagnosis of active TB were following Chinese diagnostic criteria for tuberculosis (WS288–2008), WHO guidelines for treatment of tuberculosis (fourth edition), and other references [10–12]. Active TB cases were classified as definite TB and probable TB, the definition and category of study population were listed below:…”

Section: Methodsmentioning

confidence: 99%

Indicators for prediction of Mycobacterium tuberculosis positivity detected with bronchoalveolar lavage fluid

et al. 2018

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BackgroundThe diagnosis of active pulmonary tuberculosis (TB) remains a challenge in clinic, especially for sputum negative pulmonary TB. Bronchoalveolar lavage fluid (BALF) has higher sensitivity than sputum for detection of Mycobacterium tuberculosis (Mtb). However, bronchoscopy is invasive and costly, and not suitable for all patients. In order to make TB patients get more benefit from BALF for diagnosis, we explore which indicator might be used to optimize the choice of bronchoscopy.MethodsA total of 1539 sputum-smear-negative pulmonary TB suspects who underwent bronchoscopy were recruited for evaluation. The sensitivity, specificity and accuracy of Mtb detection in sputum and BALF were compared. Odds ratios and 95% confidence intervals were used to assess variables that associated with positive acid-fast bacilli (AFB) smear, Mtb culture and nucleic acid amplification test (NAAT) of BALF in sputum-negative and non-sputum-producing pulmonary TB suspects.ResultsBALF has significantly higher sensitivity (63.4%) than sputum (43.5%) for Mtb detection by culture and NAAT. 19.7% (122/620) sputum-negative and 40.0% (163/408) non-sputum-producing suspects had positive bacteriological results in BALF. Among sputum-negative and non-sputum-producing pulmonary TB suspects, the positivity of Mtb detection in BALF is associated with a younger age, the presence of pulmonary cavities and a positive result of interferon-gamma release assay (IGRA). Sputum-negative patients under 35 years old with positive IGRA and pulmonary cavity had 84.8% positivity of Mtb in BALF.ConclusionsOur study indicated that combination of age, the presence of pulmonary cavity, and the result of IGRA is useful to predict the positivity of Mtb detection in BALF among sputum-negative and non-sputum producing pulmonary TB suspects. Those who are under 35 years old, positive for the presence of pulmonary cavity and IGRA, should undergo bronchoscopy to collect BAFL for Mtb tests, as they have the highest possibility to get bacteriologically confirmation of TB.Electronic supplementary materialThe online version of this article (10.1186/s40249-018-0403-x) contains supplementary material, which is available to authorized users.

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“…Compared to measurements directly in sera, Mtb antigen‐induced profiles (in cell or whole blood supernatants) led to less discriminatory results. Interestingly, a TB biosignature based on the relative levels of seven serum markers (C‐reactive protein, transthyretin, IFN‐γ, complement factor H, apolipoprotein‐A1, inducible protein‐10 (IP‐10) and serum amyloid A) seems promising . Efforts are now ongoing to incorporate these into simple to use and field–friendly, lateral flow based point‐of‐care tests .…”

Section: Bm For Diagnosing Active Tbmentioning

confidence: 99%

Update on tuberculosis biomarkers: From correlates of risk, to correlates of active disease and of cure from disease

et al. 2018

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Tuberculosis (TB) remains a devastating disease, yet despite its enormous toll on global health, tools to control TB are insufficient and often outdated. TB Biomarkers (TB-BM) would constitute extremely useful tools to measure infection status and predict outcome of infection, vaccination or therapy. There are several types of TB-BM: Correlate of Infection; Correlate of TB Disease; Correlate of Increased Risk of Developing Active TB Disease; Correlate of the Curative Response to Therapy; and Correlate of Protection (CoP). Most TB-BM currently studied are host-derived BM, and consist of transcriptomic, proteomic, metabolomic, cellular markers or marker combinations ('signatures'). In particular, vaccine-inducible CoP are expected to be transformative in developing new TB vaccines as they will de-risk vaccine research and development (R&D) as well as human testing at an early stage. In addition, CoP could also help minimizing the need for preclinical studies in experimental animals. Of key importance is that TB-BM are tested and validated in different well-characterized human TB cohorts, preferably with complementary profiles and geographically diverse populations: genetic and environmental factors such as (viral) coinfections, exposure to non-tuberculous mycobacteria, nutritional status, metabolic status, age (infants vs children vs adolescents vs adults) and other factors impact host immune set points and host responses across different populations. In this study, we review the most recent advances in research into TB-BM for the diagnosis of active TB, risk of TB development and treatment-induced TB cure.

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Diagnostic performance of a seven-marker serum protein biosignature for the diagnosis of active TB disease in African primary healthcare clinic attendees with signs and symptoms suggestive of TB

Cited by 134 publications

References 38 publications

Detection of a combination of serum IgG and IgA antibodies against selected mycobacterial targets provides promising diagnostic signatures for active TB

Detection of a combination of serum IgG and IgA antibodies against selected mycobacterial targets provides promising diagnostic signatures for active TB

Indicators for prediction of Mycobacterium tuberculosis positivity detected with bronchoalveolar lavage fluid

Update on tuberculosis biomarkers: From correlates of risk, to correlates of active disease and of cure from disease

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